Clinical and translational discovery最新文献

{"title":"Impacts of molecular drivers in aortic dissection","authors":"Cuihong Tian,&nbsp;Yequn Chen,&nbsp;Xuerui Tan","doi":"10.1002/ctd2.323","DOIUrl":"https://doi.org/10.1002/ctd2.323","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Aortic dissection (AD) is a lethal cardiovascular emergency involving high mortality and disability. However, its specific pathogenesis remains to be elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A bibliometric analysis based on the Web of Science database, VOSviewer software and Citex platforms was conducted to have a knowledge of the development trends, frontiers and hot spots of AD. Subsequently, the top five AD-related genes from the titles and abstracts of published literature were searched. Lastly, the roles of the top five genes and their encoded proteins in the onset of AD were reviewed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The bibliometrics showed that most studies are exploring the molecular drivers related to AD, especially gene mutations. The top five AD-related genes were transforming growth factor-β (<i>TGFB</i>)-related genes, elastin (<i>ELN</i>), fibrillin-1 (<i>FBN1</i>), angiotensinogen (<i>AGT</i>) and matrix metalloproteinase 9 (<i>MMP9</i>). In particular, regulation of the structure of elastic fiber by <i>TGFB-</i>related genes<i>, ELN</i> and <i>FBN1</i>, appears to be the principal mechanism contributing to AD onset. Activation of the renin-angiotensin system is the principal mechanism by which <i>AGT</i> triggers AD. <i>MMP9</i> promotes the formation and development of AD by degrading extracellular matrix components.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p><i>TGFB, ELN, FBN1, AGT</i> and <i>MMP9</i> are the five top molecular drivers of AD, providing a comprehensive mechanistic insight into AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141488400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomics integrates digital imaging for head and neck cancer diagnosis","authors":"K. N. ArulJothi,&nbsp;A. B. Nidhu,&nbsp;Anand Krishnan","doi":"10.1002/ctd2.307","DOIUrl":"https://doi.org/10.1002/ctd2.307","url":null,"abstract":"<p>Cancers that can manifest in the oral cavity, nasal cavity, larynx, pharynx, sinuses, and other head and neck areas are collectively called “head and neck cancers” (HNC). HNC can be broadly classified into five types: salivary gland; oral and oropharyngeal; nasal cavity and paranasal sinus; nasopharyngeal, and laryngeal and hypopharyngeal cancers. HNC accounts for one million new diagnoses annually, making it the seventh most common form of the disease globally. Among all HNCs, 90% are head and neck squamous cell carcinoma (HNSCC) which is highly heterogenous, relapsing, and metastatic with poor survival. Despite the availability of new treatments, the five-year survival rate for HNSCC patients has been reported to be approximately 50%. An early diagnosis may increase the disease management and outcomes, but it is challenging to detect smaller-sized lesions and differentiate malignant and non-malignant lesions with the available tools. Current circumstances demand an improvement in existing diagnostic strategies and the advent of novel diagnostic tools.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141435596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"THZ1: Towards KRAS mutation-based precision medicine against pancreatic ductal adenocarcinoma","authors":"Yansong Qin,&nbsp;Mancang Gu,&nbsp;Yan Shi,&nbsp;Lei Huang","doi":"10.1002/ctd2.321","DOIUrl":"https://doi.org/10.1002/ctd2.321","url":null,"abstract":"<p>Pancreatic ductal adenocarcinoma (PDAC) remains a formidable global challenge, with a grim prognosis and limited treatment options.<span>¹</span> Prior to the advent of molecular targeted therapies, patients with PDAC typically received chemotherapy and surgical resection, with limited efficacies.<span>²</span> Genetic analyses have revealed that <i>KRAS</i> mutation importantly drives the pathogenesis of PDAC, prompting an increasing number of investigations into the potential of targeted therapies addressing this genetic alteration.<span>^{3, 4}</span> Recent advances in molecular targeted therapies, in particular Cyclin Dependent Kinase inhibitors, have shown promise in preclinical studies.<span>^{5, 6}</span></p><p>The recent study by Huang et al.<span>⁷</span> presented a compelling application for the targeted agent THZ1, a small-molecule covalent CDK7/12/13 inhibitor, and provided intriguing insights into its efficacy. THZ1 demonstrated differential inhibitory effects based on specific <i>KRAS</i> mutant subtypes and showed selective efficacy against PDAC harbouring the <i>KRAS-G12V</i> mutation compared to cancer with the <i>KRAS-G12D</i> mutation.</p><p>Huang et al.’s study<span>⁷</span> employed a combination of in vitro and in vivo models to demonstrate that THZ1 was more effective in inhibiting <i>KRAS-G12V</i> PDAC. The importance of the PI3K/AKT/mTOR signalling pathway in <i>KRAS</i> mutation-driven pancreatic cancer has been previously highlighted.<span>⁸</span> A previous study<span>⁹</span> showed that in Ewing sarcoma, THZ1 reduced the phosphorylation of RNA polymerase II (RNAPOLII) by inhibiting CDK7 activity, which attenuated transcriptional activity, and that THZ1 inhibited the PI3K/AKT/mTOR signalling pathway by affecting the binding of H3K27ac to <i>PIK3CA</i>, which encodes the catalytic subunit of PI3K.</p><p>The present study<span>⁷</span> further explored how THZ1 differentially inhibited PDAC cells by affecting this pathway: THZ1 inhibited <i>KRAS-G12V</i> PDAC cells through the inhibition of RNAPOLII phosphorylation, <i>PIK3CA</i> activity, and AKT and mTOR phosphorylation, with enhanced PTEN expression, thus weakening the proliferation of cancer cells. This specificity represents a significant advance, as it paves the way for personalized management of PDAC.</p><p>The study<span>⁷</span> discovered that the discrepancies in the sensitivity of different PDAC subtypes to THZ1 were related to the differential effects of THZ1 on the activity of super-enhancers (SEs). THZ1 significantly inhibited the activity of SEs marked by H3K27ac, which bound to <i>PIK3CA</i>, in PDAC cells with the <i>KRAS-G12V</i> mutation, whereas it had a minor effect on SEs in cells with the <i>KRAS-G12D</i> mutation.</p><p>Huang et al.’s study<span>⁷</span> is of particular interest, given the critical role of <i>KRAS</i> mutatio","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.321","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneous nuclear ribonucleoprotein A2/B1, a key regulator of myocardial fibrosis","authors":"Ji-Hoon Jeong,&nbsp;Kayode Abidemi John,&nbsp;Juyeong Hong,&nbsp;Ji Hoon Lee","doi":"10.1002/ctd2.319","DOIUrl":"https://doi.org/10.1002/ctd2.319","url":null,"abstract":"<p>Heart failure is the final symptom of most cardiovascular diseases with a poor prognosis and remains a major cause of death in the United States for 100 years. Myocardial fibrosis (MF), which occurs during the evolution of heart failure, is associated with almost all forms of heart disease. MF is specified by the excessive accumulation or deposition of extracellular matrix (ECM), such as fibrillar collagen, in the myocardial tissue cells, consequently resulting in increased matrix stiffness and abnormalities in normal heart function. Cardiac fibroblast is the primary cell type responsible for the deposition of ECM in the heart, regulating the proliferation of cardiomyocytes, and maintaining the integrity of the matrix network.<span>^1-3</span> Certain pathological conditions cause fibroblast activation and collagen secretion, eventually leading to cardiac fibrosis.<span>^{3, 4}</span> However, the underlying molecular and cellular mechanisms of cardiac remodelling and dysfunction in heart failure still require further research.</p><p>The heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1), a member of the hnRNP family, is a nuclear m⁶A reader recognizing m⁶A modification in a subset of primary microRNAs (pri-miRNAs).<span>⁵</span> The hnRNPA2B1 interacts with DiGeorge syndrome critical region 8 (DGCR8), an essential component of the pri-miRNA processing complex, and mediates the processing of pri-miRNAs containing m⁶A modification.<span>⁵</span> In the acute myocardial infarction and MF, m⁶A regulators including hnRNPA2B1 are highly upregulated, and the dysregulated m⁶A signalling is significantly associated with the infiltration of immune cells, suggesting the role of m⁶A in the development of cardiovascular disease.<span>⁶</span> The recent investigation led by Li et al. demonstrated that hnRNPA2B1, a key regulator of MF, regulates the miR-221-3p/Foxo4-mediated inflammatory response and the proliferation of cardiac fibroblasts.<span>⁷</span> This study group found that hnRNPA2B1 is also upregulated in MF in an isoproterenol (ISO)-induced model and ISO-treated primary cardiac fibroblasts. The deletion of hnRNPA2B1 significantly diminished the ISO-induced inflammatory infiltration and collagen deposition as well as the cardiac fibroblast proliferation and activation. Furthermore, they found hnRNPA2B1-regulated miRNAs (miR-210, miR-99b and miR-221) in MF. More importantly, they demonstrated that Foxo4, one of the widely expressed forkhead box (Fox) transcription factor O family members, is a target of miR-221-3p of hnRNPA2B1 and hnRNPA2B1/miR-221-3p/Foxo4 axis regulates inflammatory response and myofibroblast activation in the development of MF.</p><p>In conclusion, elucidating the role of hnRNPA2B1 as a key regulator of cardiac fibrosis is crucial to demonstrate a new molecular mechanism regulating inflammatory ","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning for predicting synergistic drug combinations: State-of-the-arts and future directions","authors":"Yu Wang,&nbsp;Junjie Wang,&nbsp;Yun Liu","doi":"10.1002/ctd2.317","DOIUrl":"https://doi.org/10.1002/ctd2.317","url":null,"abstract":"<p>Combination therapy has emerged as an efficacy strategy for treating complex diseases. Its potential to overcome drug resistance and minimize toxicity makes it highly desirable. However, the vast number of potential drug pairs presents a significant challenge, rendering exhaustive clinical testing impractical. In recent years, deep learning-based methods have emerged as promising tools for predicting synergistic drug combinations. This review aims to provide a comprehensive overview of applying diverse deep-learning architectures for drug combination prediction. This review commences by elucidating the quantitative measures employed to assess drug combination synergy. Subsequently, we delve into the various deep-learning methods currently employed for drug combination prediction. Finally, the review concludes by outlining the key challenges facing deep learning approaches and proposes potential challenges for future research.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The therapeutic potential of interleukin-2/anti-interleukin-2 antibody complex in cold storage-associated kidney transplantation","authors":"Yao Xia,&nbsp;Jiefu Zhu","doi":"10.1002/ctd2.302","DOIUrl":"https://doi.org/10.1002/ctd2.302","url":null,"abstract":"<p>The incidence of end-stage renal disease (ESRD) is gradually increasing worldwide, with a 107% increase in the United States from 2000 to 2019.<span>¹</span> Compared to hemodialysis and peritoneal dialysis, kidney transplantation significantly reduces mortality rates and improves the quality of life for ESRD patients, making it the preferred form of renal replacement therapy. However, the glaring disparity between the demand for kidney donors and their availability persists. Consequently, we have to expand the criteria for using donor kidneys. However, such kidneys are often from older donors, those with hypertension, or those from patients who have undergone cardiopulmonary resuscitation. The short-term recovery and long-term prognosis of these donor kidneys face significant challenges. Among them, delayed graft function (DGF) is a common complication that affects prognosis.<span>²</span> DGF is defined as the requirement for dialysis within the first week following transplantation and is indicative of significant acute tubular necrosis. IRI, which refers to damage caused when blood flow is restored to an ischemic organ, can lead to DGF, primary non-function and even loss of the transplanted kidney, significantly impacting early functional recovery and long-term survival of the transplant.<span>³</span></p><p>In kidney transplantation, the warm and cold ischemic injuries to the transplanted kidney are unavoidable. Warm ischemia time is defined as the duration between the cessation of donor blood supply to an organ and the initiation of cold perfusion, while cold ischemia time refers to the period during which grafts are stored in a cold organ preservation solution.<span>⁴</span> The mouse kidney transplantation with prolonged cold ischemia time is a suitable model, although it cannot fully replicate the clinical processes of human transplantation. Notably, human kidney grafts can withstand 24 h of cold ischemia, while mouse kidney grafts can tolerate a maximum of 10 h of cold ischemia, with varying degrees of maladaptive repair observed post-transplantation.<span>^{5, 6}</span></p><p>Regulatory T cells (Tregs) represent a subset of CD4+ T cells, which are categorized into three classes based on their origin and differentiation pathways. Among these, Tregs derived from immature T lymphocytes during thymic development, characterized by the CD4+ CD25+ Foxp3+ phenotype, are commonly utilized in research.<span>⁷</span> The application of Tregs in the field of solid organ transplantation is particularly relevant to the goal of achieving tolerance, aiming to reduce or eliminate the need for immunosuppressive drugs while maintaining tissue repair and managing acute rejection responses. A key challenge in the clinical use of Tregs is how to effectively expand their numbers, whether by increasing the number of endogenous Tregs or through the direct infusion of exogenously expanded Tregs.<s","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.302","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The clinical application and laboratory management of molecular genetic diagnosis in children's hospital","authors":"Wenjie Bao,&nbsp;Qihua Fu,&nbsp;Xiaoqing Zhang,&nbsp;Xi Mo,&nbsp;Tingting Yu","doi":"10.1002/ctd2.315","DOIUrl":"https://doi.org/10.1002/ctd2.315","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Molecular diagnostic technology is the foundation of precision medicine, which has the advantages of good specificity, high sensitivity, strong targeting, rapiddiagnosis, etc. It has a wide range of applications in the field of pediatrics. However, molecular diagnostic technology is characterized by complicated experimental operation, high difficulty in data analysis and interpretation, in consistent standards among laboratories, and difficult standardization of technical processes. Enhancing the application value of molecular diagnostic technology in pediatrics and promoting the high-quality development of the discipline requires careful consideration by relevant management and professionals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study firstly outlines the development history of molecular diagnostic technology. Then, it analyzes the application of molecular diagnostic technology in the field of pediatrics. Finally, it explores the countermeasures for the management of molecular diagnostic laboratories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study highlights the importance of molecular diagnostic technology in providing information and decision-making basis for disease prevention, prediction,diagnosis, treatment and regression. It has a wide range of applications in the molecular diagnosis of pediatric hereditary diseases, malignant tumors and infectious diseases. In addition, the countermeasures for the management of molecular diagnostic laboratories are proposed from the five aspects of laboratory, personnel team construction, standardized management,multidisciplinary cross-discipline, research and translation, safety managementand ethical supervision, and management upgrading and modernization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Molecular diagnostic technology, as the basis of precision medicine, has become one of the important frontier fields in the development of contemporary pediatric medicine. Enhanced laboratory capacity in molecular diagnostic techniques can improve outcomes in the prevention, prediction, diagnosis, treatment, prognosis and research of pediatricdiseases, and lay the groundwork for child healthcare.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmaceutical company payments to Japanese breast cancer practice guideline authors","authors":"Anju Murayama,&nbsp;Kenichi Higuchi,&nbsp;Keerthana R. Byreddy,&nbsp;Kugo Hinari,&nbsp;Yuki Senoo","doi":"10.1002/ctd2.304","DOIUrl":"https://doi.org/10.1002/ctd2.304","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The creation of breast cancer practice guidelines requires proper management of financial relationships with drug companies, as they can introduce conflicts of interest (COIs) among guideline authors. However, little is known about the specific landscape and fraction of financial interactions between the authors of the Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer, edition 2022 (JBCS2022) and drug companies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using payment data publicly disclosed by major drug companies in Japan, this study analysed the personal payments made to the authors of JBCS2022 between 2016 and 2020. We performed descriptive analyses on the payment data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 149 JBCS2022 authors, 115 (77.2%) received at least one personal payment totaling $3 828 455 from drug companies between 2016 and 2020. The average and median payment amounts per author were $25 772 (standard deviation: $58 197) and $2761 (interquartile range: $322‒$15 828), respectively. The total annual payments per JBCS2022 authors between 2016 and 2019 increased from $588 054 in 2016 to $967 802 in 2019. The JBCS2022 chairperson and vice-chairperson received $246 936 (fourth highest) and $216 744 (fifth highest) over the 5 years. More than 60% of personal payments to the JBCS2022 authors were not declared by the authors as they were below the declaration threshold set by the Japanese Breast Cancer Society. However, nine authors undeclared personal payments summing $594 615 even though these payments were higher than the thresholds.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrated that the majority of the breast cancer guideline authors received personal payments from drug companies in Japan. Furthermore, the majority of payments were not declared because of the less transparent COI policy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141326509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel roles of the junctional protein associated with coronary artery disease in regulating Hippo-YAP signalling axis to improve liver regenerative potential","authors":"Eltyeb Abdelwahid","doi":"10.1002/ctd2.306","DOIUrl":"https://doi.org/10.1002/ctd2.306","url":null,"abstract":"<p>The Hippo/Yap signalling pathway is known to be a conserved pathway that controls organ size by promoting tissue regeneration, however, the mechanism is not fully understood. Emerging experimental research has characterized various roles by which the Hippo mechanism promotes the regenerative capacity of distinct mouse organs such as the intestine, heart and the liver, nevertheless, attempts for therapeutic applications require additional efforts to avoid potential adverse effects. The junctional protein associated with coronary artery disease (JCAD) has been proposed as a new potential therapeutic target in medical conditions, mainly cardiovascular disease. Recently, it has been demonstrated that JCAD negatively regulates Hippo signalling, leading to the activation of YAP (yes-associated protein), the transcriptional effector of the pathway.<span>¹</span> Zhang and colleagues report novel results of JCAD in regulating liver regeneration in mice subjected to partial hepatectomy (PH) to model patients undergone liver resection or transplanted with small-for-size graft.<span>²</span> Using both global JCAD knockout (JCAD-KO) and conditional JCAD knockout mice, they found decreased expression of genes involved in the cell cycle and impaired DNA replication. Moreover, JCAD deficiency in hepatocytes causes prolongation of the cell cycle due to G2/M transition blockage. When they overexpressed or replenished JCAD in JCAD KO primary hepatocytes, they were able to reverse cell cycle duration, which was abolished by administering the YAP inhibitor, verteporfin. The paper demonstrates that JCAD promotes cycle-dependent hepatocellular regeneration. The dramatic progress being made in the field makes the idea of expanding these findings more tempting. The proposed role of JCAD in liver regeneration opens new avenues for determining potential targets required for therapeutic approaches based on modulation of the cell-cycle machinery.</p><p>Previous works of the Hippo/YAP1 pathway have delineated numerous associations of this pathway with human diseases with a wide array of cellular functions.<span>³</span> An interesting finding is learned from the result that JCAD competed with LATS2 for WWC1 interaction, causing inhibition of LATS2 and YAP activation, and enhanced expression of cell cycle regulatory genes. The mechanistic insights on how cell cycle gene expression integrates with each step of controlling regeneration in the liver will need to be investigated from broader aspects including the development of novel experimental tools required for both the prevention and improvement of different pathologies, with special emphasis on regeneration, transplantation and bioengineering. Sophisticated cell cycle manipulation approaches together with the understanding of how specific genomic regions or configurations respond to cell cycle modulation may precisely control cell fate.</p><p>Interestingly, JCAD expression is mainly loca","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141329373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered cell versus modified exosomes in cancer therapy","authors":"Rajib Dhar,&nbsp;Arikketh Devi","doi":"10.1002/ctd2.320","DOIUrl":"https://doi.org/10.1002/ctd2.320","url":null,"abstract":"<p>Cancer therapeutic development is the most challenging domain in cancer. Cell-based cancer therapeutics come up with promising effectiveness. This approach was also cell-modified for better targeting efficiency development. Cell engineering-based cancer therapeutic is a cutting-edge method in cancer therapy. Due to complications of this process, cost and post-treatment side effects, this phenomenon came into the question mark. In this scenario, extracellular vesicle (EVs) research introduces a cell-free cancer therapeutic approach. In the therapeutic aspect most used EVs, come from stem cells, plants, and engineered cells. Among several EVs populations, Exosomes are the most used worldwide cell-free therapeutic tool for ageing cancer. The most interesting facts about exosomes are the biocompatible, non-immunoreactive, cross-biological barrier, and non-toxic (depending on the parental cell's nature). In this article, we are exploring modified exosomes (biological or chemical) that create a remarkable outcome in cancer therapeutic development compared to engineered cell-based therapeutics. Hope, in the future, modified exosomes become an effective, affordable, and specific cancer-targeting precision medicine.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.320","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141315445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}